Van Hooijdonk was born in Steenbergen. His Moroccan biological father left Van Hooijdonk's mother before his birth. He grew up in a small village nearby Steenbergen named Welberg. While playing in one of SC Welberg's youth squads Van Hooijdonk became familiar with football. His favourite team was NAC Breda and he was already watching their games at a young age. When he was 11 years old he took part in a talent pool on the open day of the team and he impressed the NAC scouts. He was asked to join NAC, which he did and played mainly as a right midfielder. When he was 14 he was told he was not good enough for NAC and he switched to amateur side. Here he switched to the striker position and he would play five years for the team, of which the last two seasons in their first team.
As RBC were facing financial trouble in these days they were forced to use youth players faster than other teams and in the 1988–89 season Van Hooijdonk was brought in as a substitute for a few times and soon scored three goals, which resulted in more appearances throughout the season. Because RBC's main striker suffered from an injury Van Hooijdonk played almost the whole second half of the season, scoring a total of six goals in 32 matches. He signed his first professional contract and his final breakthrough came in the following season in which he became a key player for the team, scoring 27 times in 37 matches. Several teams showed interest and NAC Breda was one of the teams. Van Hooijdonk did not hesitate and signed a contract at the team he supported as a child.
NAC paid 4 guilders for Van Hooijdonk, a player whom they had sent away while he was playing in their youth squads. Returning at NAC gave him a good feeling and he was determined to show them what he was capable of. Van Hooijdonk succeeded in his goal and scored a total of 81 goals in four seasons, in which he played 115 matches. He helped the team to win promotion to the Eredivisie in 1993. In his last season at this club, in December 1994, he was called up for the Netherlands for the first time in his career. He set scoring streak 11 Eredivisie matches. Not much later, in the 1994–95 winter break, Celtic offered him a contract and made a deal with NAC for him to join them immediately, which he accepted.
Van Hooijdonk made his Celtic debut on 11 January 1995 in a league match against Hearts at Hampden Park. The big striker made an instant impact for his new team by scoring a stunning opening goal. Alas, Hearts went on to equalise and the game finished 1–1. However, Van Hooijdonk settled quickly at Celtic and he became an instant favourite with the fans. When Van Hooijdonk arrived at Celtic they had not won any trophies in six years. However with Van Hooijdonk Celtic won the Scottish Cup right away and Van Hooijdonk was the only goalscorer in the final against Airdire in May 1995. The following season, 1995–96, saw Van Hooijdonk in outstanding form for Celtic. He scored 32 goals, including 26 in the League which saw him finish top scorer. Of particular note was Van Hooijdonk's prowess at scoring from free kicks. However, despite Van Hooijdonk's goals and the attractive football being played by manager Tommy Burns' side, Celtic still finished the season without any silverware. Van Hooijdonk's last season at Celtic, 1996–97, was an unhappy time for both the player and the club. A row with the Celtic chairman/owner, Fergus McCann, would rumble on through the year and as a result he often ended up on the substitute bench. The manager of the Dutch national team Guus Hiddink told him he would not be selected for the national team as long as he was not a regular first team player at Celtic.
In total Van Hooijdonk scored 52 goals for Celtic in 84 appearances. He eventually left Celtic over a wage dispute towards the end of the 1996–97 season, stating that the reputed £7,000 a week rise he was being offered might be "good enough for the homeless" to live on "but not for an international striker." He went on to join Nottingham Forest in a deal worth up to £4.5 million.
Van Hooijdonk arrived as Forest were in deep relegation trouble, struggling to maintain their position in the Premier League. He made his debut for Forest in a 1–1 draw against Blackburn on 11 March 1997. It was hoped the arrival of van Hooijdonk would kick-start their survival, but he scored just one goal in his eight games for them that season. Although only one of those games was lost, the other seven were drawn and Forest were relegated. He immediately pledged his future to helping the club regain their status. The following season was an unqualified success, both for him and Forest. Forest won the title and promotion in a competitive league (facing stiff opposition from Sunderland, Charlton and Middlesbrough), with van Hooijdonk scoring 34 goals and building up a good partnership with strike partner Kevin Campbell, who scored 23 times. He was a regular in the Dutch national squad, and was named in the Dutch squad for 1998 FIFA World Cup in France where he scored as a substitute in the match against South Korea.
After the World Cup had finished he discovered that the promised strengthening to the Forest squad to enable them to cope back in the Premier League had not transpired, indeed that his strike partner Campbell (who had an ongoing back injury) had been sold to Trabzonspor for £2.5m. The club had also announced that Scot Gemmill was dropped from the first team for refusing to sign a new contract, and that club captain and terrace hero Colin Cooper was being allowed to leave to the team promoted alongside them as runners up, Middlesbrough. Van Hooijdonk asked for a transfer. The club's new owners refused. Van Hooijdonk announced that he had been told previously that he could leave the club at the end of the 1997/98 season if he so wished, that he felt betrayed by the club's owners who had failed to deliver on their promises to him regarding the strengthening of the team, and that he felt he could no longer play for his employers. His employers, desperate for a striker, refused to allow him to be transfer-listed again, so van Hooijdonk announced his intention to strike. He kept fit by training with his former club NAC Breda. Because of his behaviour Van Hooijdonk received criticism both from fans and from his teammates, not least from Steve Stone and manager Dave Bassett. The club refused to listen to offers for him, as they needed a top striker and the stand-off lasted until early November when he, realising that he had no choice, agreed to return. By this time the club was again in relegation trouble being bottom of the league without a win in nine games, having a striker would have helped. He played sporadically between then and the end of the season, outlasting Dave Bassett and Steve Stone. He scored 6 goals in his 19 starts in the Premier League, including his first goal in his third game back against Forest's fierce rivals Derby County, helping them to a draw. Infamously after this goal most of his teammates refused to celebrate alongside him, instead going to Scot Gemmill, the man who crossed the ball to him. He also scored a last minute home equaliser against rivals Liverpool with a trademark free-kick that protected Forest's proud unbeaten home run against them that goes back to the 1980s. Forest ended the 1998/99 Premier League season bottom and were relegated.
At the end of the 1998/99 season he returned to the Netherlands with Vitesse Arnhem in a £3.5m move to continue his career after and did much to convince his critics of his goal-scoring abilities when he helped the Arnhem team to a UEFA Cup spot with 25 goals in one season. He also returned into the Dutch national team in this period. Van Hooijdonk then signed a three-year deal for Benfica in 2000 where he joined up with one of the former Celtic F.C. 'three amigos' Jorge Cadete. He eventually only played one season for them with 19 goals. At Benfica he faced the same structural problems as he faced at Nottingham Forest and the team used three different managers throughout the season. The new chairman at the club had no faith in Van Hooijdonk and he was set back into their second team. Benfica were planning on selling him to another foreign club, but all Van Hooijdonk wanted was to return to his home country. At the end of the 2000/01 season, he signed for his fourth Dutch club, Feyenoord Rotterdam.
Never one to settle down, van Hooijdonk joined Fenerbahçe SK at the beginning of the 2003–04 season where he featured in 52 games for the Turkish club and scored 32 goals (24 in his first season). He was nicknamed Aziz Pierre (means Saint Pierre in Turkish) by fans. He wore the number 17, the same number that he worn for the national team. He won the Süper Lig title in 2003–04 (first championship in his career) and again the following year in 2004–05 with Fenerbahçe.
In mid-2005, he signed again for his former club, NAC, playing 17 games but scoring only 5 goals. During the winter transfer window of the 2005/06 season, he signed for another former club, Feyenoord, where he scored 8 goals in 37 appearances. On 17 October 2006 Van Hooijdonk announced his retirement at the end of the 2006–07 season. On 13 May 2007 he eventually played his final professional match after a draw with Feyenoord against FC Groningen in the play-offs, having played 550 games (335 goals) in the highest leagues in 18 seasons of professional football.
It was reported on 29 May 2008 that van Hooijdonk had been a victim of fraud and had lost £2,000,000 to a scam, which involved him investing in a Chinese textile company which did not exist. Dutch police said the scam was worth 'many millions of euro'.